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Abstract Background Civil society organizations (CSOs) are important in health care delivery. They have the potential to play significant roles in immunization-related services, such as advocacy, health education, demand creation and resource mobilization. Their roles are often indispensable, diverse and beneficial in reducing infant morbidity and mortality due to vaccine-preventable diseases. This study explored the potential barriers to and facilitators of CSO engagement in increasing immunization coverage in Odukpani Local Government Area of Cross River State, Nigeria. Methods The study adopted qualitative data collection methods. Twenty-two focus group discussion (FGD) sessions, three in-depth interviews (IDIs) and 26 key informant interviews (KIIs) were conducted. Appropriate guides (FGD guide, IDI guide and KII guide) were used to conduct face-to-face interviews and the discussions. The FGDs, KIIs and IDIs were audio-recorded and transcribed. A framework analysis approach involving five key stages of analysis (familiarization with data, identification of thematic framework, indexing, charting, mapping/interpretation) was used for data analyses and presentation. Results CSOs encounter barriers in the course of their immunization advocacy, communication and social mobilization due to male child preference, leading to shielding of male children and not allowing them to be given immunization, as well as patriarchy, safety concerns, religious concerns, anti-vaccine misinformation and rumours, low perception of effectiveness and efficacy of vaccines, inaccessibility of localities, low health literacy and superstitious beliefs. Various community structures, such as the institution of the village head, elders’ council and town crier (announcer), and the existence of change agents, act as facilitators of immunization advocacy and uptake. Factors such as traditional control mechanisms including masquerades and religion act as either barriers or facilitators depending on the community and the mode of deployment. CSO members are willing to overcome these barriers and leverage the facilitators. Conclusions For successful engagement in immunization-related services, there are barriers in the study area that CSOs should overcome, such as male child preference and geographic inaccessibility, as well as facilitators that they should leverage such as traditional information dissemination systems and enforcement of compliance by the chiefs and elders’ council.